Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:6.2.1.7 (BAL)
1,977 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The BAL technique was used to assess the pulmonary injury of coal dust and rock dust in Huai-Nan coal mine in Anhui Province. Dust suspended in saline and dust-free supernatant were instilled intratracheally to Wistar rats and Syrian hamsters. Saline was used in treating controls. The animals were sacrificed 24 h after treatment, their lungs were lavaged, and pulmonary damage was evaluated by cellular and biochemical assays of lavage fluid. Pulmonary injury was expressed by the cell toxicity index (CTI). CTI is the product of the number of times of meaningful parameters for treated groups compared to controls (LDH, acid phosphatase, and polymorphonuclear neutrophils in this case). The CTI values were found to be 5.19, 2.28, and 5.15 for rock dust, coal dust, and Shanghai suspended particulates, respectively. The toxicity of rock dust is higher than that of coal dust, but is similar to that of Shanghai suspended particulates. The cell toxicity of dust suspension solution is higher than that of dust-free supernatant. CTI can be used as an indicator of the relative toxicity of respirable dusts in in vivo studies.
...
PMID:Pulmonary injury in laboratory animals induced by Huai-Nan coal mine respirable dust. 327 May 14

It has been shown that oxophenylarsine (PhAsO) inhibits glucose uptake in MDCK cells. In addition to the known impairment of cellular energy metabolism, this inhibition may contribute to the acute toxicity of trivalent organic arsenicals. We have investigated the effect of BAL, DMPS, DMSA, and other sulfur compounds on cellular incorporation of [U-14C]PhAsO and their efficacy to revert PhAsO-induced inhibition of glucose uptake. In the presence of [U-14C]PhAsO (2 microM), the radiolabel was steadily accumulated by the cells over 150 min without any signs of severe cell damage (e.g., altered morphology, increased LDH release). A notable decrease of cellular ATP was only observed at 150 min, whereas within 30 min uptake of D-[6-(14)C]glucose was reduced to 40% of controls. When BAL, DMPS, or DMSA was added after 30 min, the inhibition of glucose uptake was reversed, accompanied by a decrease in cell-associated radiolabel from [U-14C]-PhAsO. Water-soluble DMPS and DMSA required longer times than BAL for comparable effects. 2,3-Bis(acetylthio)propanesulfonamide, a thioester derivative, and dithiothreitol, a 1,4-dithiol, were effective only with the highest concentration tested (200 microM). 2-Mercaptoethanol neither reversed inhibition of glucose uptake nor influenced [U-14C]PhAsO incorporation. Our results show that inhibition of glucose uptake is a very early event in PhAsO cytotoxicity which occurs before any decrease of cellular energy metabolism and/or full cellular loading with arsenic comes into effect. The more rapid onset of action of lipophilic BAL compared to PhAsO action.
...
PMID:Reversal of oxophenylarsine-induced inhibition of glucose uptake in MDCK cells. 758 19

Pneumocystis carinii pneumonia (PCP) in HIV-infected patients remains a life-threatening complication in the course of HIV infection. Despite effective treatment, mortality may still be as high as 10%. The identification of risk factors associated with a lethal outcome might be helpful as a guide to therapy for patients at risk and in the evaluation of new drugs with anti-pneumocystic activity. In a retrospective study 58 first episodes of HIV-associated PCP without prophylaxis were analyzed. Variables associated univariately with higher mortality were identified. A prognostic rule was established in a multivariate approach using canonical discriminant analysis. Cut-off values for parameters included were determined in order to allow a clinically applicable estimate of the individual risk. Variables associated with early mortality were hemoglobin, hematocrit, platelet count, albumin, total protein, gamma-globulins, and AaDO2. LDH values, percentage of neutrophils in the BAL, as well as the cellular immunologic state as indicated by CD4-cell count were not significantly associated with the outcome. The discriminant function yielded the best classification results with the inclusion of hemoglobin, albumin, and gamma-globulins (overall accuracy 86%). Two or more of the following parameters were associated with a 14-fold increased risk of in-hospital mortality: hemoglobin less than 10 g/dl, albumin less than 3 g/dl, and gamma-globulins less than 1.2 g/dl. This prognostic rule was 80% sensitive and 94% specific with a negative predictive value of 94%, yielding an overall accuracy of 91%. Patients with HIV-associated PCP with a positive prognostic rule have a 14-fold increased risk for in-hospital lethal outcome. This discriminant rule may be helpful in identifying patients at risk.
...
PMID:Predicting in-hospital outcome in HIV-associated Pneumocystis carinii pneumonia. 855 84

The aim of the study was to extend existing evidence that intratracheal aerosolization of LPS may serve as a very relevant model to study ARDS. The authors investigated the sequence of pathogenic events reflected by changes in levels of tumor necrosis factor alpha (TNF alpha), surfactant-associated protein A (SP-A) in BAL fluid, in addition to cell count, edema formation, and respiratory function. Within 24 h following intratracheal aerosolization of LPS in the rat, ARDS could be diagnosed according to the lung injury score for patients. This score includes the extent of the inflammatory density on chest X-rays, the severity of hypoxemia, the decline in lung compliance, and the level of PEEP (positive end expiratory pressure). In addition, other typical features of human ARDS appeared to be present in this model: (1) increased microvascular permeability reflected by edema, elevated levels of protein and of LDH, and increased numbers of PMNs in BAL fluid; (2) high levels of TNF alpha in BAL fluid preceding the appearance of PMNs; (3) changes in breathing pattern and a gradual development of respiratory failure with decreased compliance. SP-A levels in BAL fluid doubled within one hour after LPS administration, suggesting that this collectin may play a role in the immediate inflammatory response. Taken together, the findings presented here suggest that intratracheal LPS administration mimics the clinical development of ARDS very closely.
...
PMID:Intratracheal aerosolization of endotoxin (LPS) in the rat: a comprehensive animal model to study adult (acute) respiratory distress syndrome. 920 56

Chronic inhalation of crystalline silica can produce lung tumors in rats whereas this has not been shown for amorphous silica. At present the mechanisms underlying this rat lung tumor response are unknown, although a significant role for chronic inflammation and cell proliferation has been postulated. To examine the processes that may contribute to the development of rat lung tumors after silica exposure, we characterized the effects of subchronic inhalation of amorphous and crystalline silica in rats. Rats were exposed for 6 h/day, on 5 days/week, for up to 13 weeks to 3 mg/m(3) crystalline or 50 mg/m(3) amorphous silica. The effects on the lung were characterized after 6.5 and 13 weeks of exposure as well as after 3 and 8 months of recovery. Exposure concentrations were selected to induce high pulmonary inflammatory-cell responses by both compounds. Endpoints characterized after silica exposure included mutation in the HPRT gene of isolated alveolar cells in an ex vivo assay, changes in bronchoalveolar lavage fluid markers of cellular and biochemical lung injury and inflammation, expression of mRNA for the chemokine MIP-2, and detection of oxidative DNA damage. Lung burdens of silica were also determined. After 13 weeks of exposure, lavage neutrophils were increased from 0.26% (controls) to 47 and 55% of total lavaged cells for crystalline and amorphous silica, with significantly greater lavage neutrophil numbers after amorphous silica (9.3 x 10(7) PMNs) compared to crystalline silica (6.5 x 10(7) PMNs). Lung burdens were 819 and 882 microg for crystalline and amorphous silica, respectively. BAL fluid levels of LDH as an indicator of cytotoxicity were twice as high for amorphous silica compared to those of crystalline silica, at the end of exposure. All parameters remained increased for crystalline silica and decreased rapidly for amorphous silica in the 8-month recovery period. Increased MIP-2 expression was observed at the end of the exposure period for both amorphous and crystalline silica. After 8 months of recovery, those markers remained elevated in crystalline silica-exposed rats, whereas amorphous silica-exposed rats were not significantly different from controls. A significant increase in HPRT mutation frequency in alveolar epithelial cells was detected immediately after 13 weeks of exposure to crystalline, but not to amorphous silica. A significant increase in TUNEL staining was detected in macrophages and terminal bronchiolar epithelial cells of amorphous silica-exposed rats at the end of the exposure period; however, crystalline silica produced far less staining. The observation that genotoxic effects in alveolar epithelial cells occurred only after crystalline but not amorphous silica exposure, despite a high degree of inflammatory-cell response after subchronic exposure to both types of silica, suggests that in addition to an inflammatory response, particle biopersistence, solubility, and direct or indirect epithelial cell cytotoxicity may be key factors for the induction of either mutagenic events or target cell death.
...
PMID:Pulmonary chemokine and mutagenic responses in rats after subchronic inhalation of amorphous and crystalline silica. 1091 Oct

Epidemiological studies of workers in weaving units in carpet industries have shown relationships between the airborne dust concentrations and pulmonary ill health. Therefore, to predict the health risk of carpet weavers, this preliminary experiment was conducted to evaluate the effect of carpet dust (knotted, tufted) on cellular and biochemical mediators considered as potential biological markers of lung injury. Lung cytoplasmic (lactate dehydrogenase, LDH), lysosomal (acid phosphatase, ACP), type II (alkaline phoshatase, ALP) and Clara-cell marker enzymes (gamma-glutamyl transferase, GGT) were monitored in rat cell-free lung lavage (BAL) during postexposure days 1, 4, 8, and 16. Furthermore, lung microsomal cytochrome P-450 (CYP450) and Clara-cell secretory protein (CC16) content in BAL was also evaluated. These pulmonary marker enzymes were significantly elevated during the postexposure period over the respective untreated control; however, tufted carpet dust shows more responses than knotted carpet dust. Lung CYP450 content was reduced significantly at early days; the pattern shows the reoccurrence of CYP450 content in the later stage of postexposure to carpet dust. Clara-cell secretory protein in BAL shows decline in the carpet-treated group; however, tufted carpet shows more decline than knotted carpet. Thus, reduction in CC16 level may have important implication in the development of chronic lung inflammation and diseases. Present investigation found that modulation of these cellular marker enzymes is clear evidence of pulmonary damage caused by exposure to carpet dust.
...
PMID:Alteration in cellular and biochemical markers of pulmonary toxicity in rat lung exposed to carpet dusts. 1295 17

In addition to being an air pollutant, NO2 is a potent inflammatory oxidant generated endogenously by myeloperoxidase and eosinophil peroxidase. In these studies, we sought to determine the effects of NO2 exposure on mice with ongoing allergic airway disease pathology. Mice were sensitized and challenged with the antigen ovalbumin (OVA) to generate airway inflammation and subsequently exposed to 5 or 25 ppm NO2 for 3 days or 5 days followed by a 20-day recovery period. Whereas 5 ppm NO2 elicited no pathological changes, inhalation of 25 ppm NO2 alone induced acute lung injury, which peaked after 3 days and was characterized by increases in protein, LDH, and neutrophils recovered by BAL, as well as lesions within terminal bronchioles. Importantly, 25 ppm NO2 was also sufficient to cause AHR in mice, a cardinal feature of asthma. The inflammatory changes were ameliorated after 5 days of inhalation and completely resolved after 20 days of recovery after the 5-day inhalation. In contrast, in mice immunized and challenged with OVA, inhalation of 25 ppm NO2 caused a marked augmentation of eosinophilic inflammation and terminal bronchiolar lesions, which extended significantly into the alveoli. Moreover, 20 days postcessation of the 5-day 25 ppm NO2 inhalation regimen, eosinophilic and neutrophilic inflammation, pulmonary lesions, and AHR were still present in mice immunized and challenged with OVA. Collectively, these observations suggest an important role for NO2 in airway pathologies associated with asthma, both in modulation of degree and duration of inflammatory response, as well as in induction of AHR.
...
PMID:Nitrogen dioxide enhances allergic airway inflammation and hyperresponsiveness in the mouse. 1608 73

Previous studies have reported little correlation between the relative toxicity of particle types when comparing lung toxicity rankings following in vivo instillation versus in vitro cell culture exposures. This study was designed to assess the capacity of in vitro screening studies to predict in vivo pulmonary toxicity of several fine or nanoscale particle types in rats. In the in vivo component of the study, rats were exposed by intratracheal instillation to 1 or 5 mg/kg of the following particle types: (1) carbonyl iron (CI), (2) crystalline silica (CS) (Min-U-Sil 5, alpha-quartz), (3) precipitated amorphous silica (AS), (4) nano-sized zinc oxide (NZO), or (5) fine-sized zinc oxide (FZO). Depending on particle type and solution state, these particles range in size from 90 to 500 nm in size. Following exposures, the lungs of exposed rats were lavaged and inflammation (neutrophil recruitment) and cytotoxicity end points (bronchoalveolar lavage [BAL] fluid lactate dehydrogenase [LDH] values) were measured at 24 h, 1 week, 1 and 3 months postexposure. For the in vitro component of the study, three different culture conditions were utilized. Cultures of (1) rat L2 lung epithelial cells, (2) primary alveolar macrophages (AMs) (collected via BAL from unexposed rats), as well as (3) AM-L2 lung epithelial cell cocultures were incubated with the particle types listed above, and the culture fluids were evaluated for cytotoxicity end points (LDH, 1-(4,5-dimethylthiazol-2-yl)-3,5-diphenylformazan [MTT]) as well as inflammatory cytokines (macrophage inflammatory 2 protein [MIP-2], tumor necrosis factor alpha [TNF-alpha], and interleukin-6 [IL-6]) at one (i.e., cytokines) or several (cytotoxicity) time periods. Results of in vivo pulmonary toxicity studies demonstrated that instilled CI particles produced little toxicity. CS particles produced sustained inflammation and cytotoxicity. AS particles produced reversible and transient inflammatory responses. NZO or FZO particles produced potent but reversible inflammation which was resolved by 1 month postinstillation exposure. Results of in vitro pulmonary cytotoxicity studies demonstrated a variety of responses to the different particle types, primarily at high doses. With respect to the LDH results, L2 cells were the most sensitive and exposures to nano- or fine-sized ZnO for 4 or 24 h were more cytotoxic than exposures to CS or AS particles. Macrophages essentially were resistant and epithelial macrophage cocultures generally reflected the epithelial results at 4 and 24 h incubation, but not at 48 h incubation. MTT results were also interesting but, except for nano- and fine-sized ZnO, did not correlate well with LDH results. Results of in vitro pulmonary inflammation studies demonstrated that L2 cells did not produce MIP-2 cytokines, but CS- or AS-exposed AMs and, to a lesser degree, cocultures secreted these chemotactic factors into the culture media. Measurements of TNF-alpha in the culture media by particle-exposed cells demonstrated little activity. In addition, IL-6 secretion was measured in CS, AS, and nano-sized ZnO-exposed cocultures. When considering the range of toxicity end points to five different particle types, the comparisons of in vivo and in vitro measurements demonstrated little correlation, particularly when considering many of the variables assessed in this study-such as cell types to be utilized, culture conditions and time course of exposure, as well as measured end points. It seems clear that in vitro cellular systems will need to be further developed, standardized, and validated (relative to in vivo effects) in order to provide useful screening data on the relative toxicity of inhaled particle types.
...
PMID:Assessing toxicity of fine and nanoparticles: comparing in vitro measurements to in vivo pulmonary toxicity profiles. 1730 Oct 66

Sepsis is still a major cause of the high mortality rate in the intensive care unit. Many studies have been published about the severity of sepsis, but the cause of mortality in sepsis and multiorgan failure is still obscure. This study investigated the effects of caffeic acid phenethyl ester (CAPE) particularly on the inflammatory and related histopathological changes in the lung, liver and kidney in an experimental sepsis model. Forty Sprague Dawley rats were used in this study, and were divided into four groups of ten rats each, as follows: Group I was given intraperitoneal saline infusion treatment. Group II was given intraperitoneal CAPE infusion treatment. Sepsis was induced in the animals in Group III (sepsis with saline infusion), while Group IV rats underwent induced sepsis plus CAPE infusion treatment (sepsis with CAPE infusion). Sampling was performed 48 h after treatment. The induction of sepsis resulted in a significant increase in serum glucose, leukocytes, urea, creatinine, LDH levels in BAL, plasma MDA, AST and ALT levels in the sepsis + saline group. The use of CAPE significantly decreased these parameters. Histopathological examination revealed less congestion, portal inflammation, and focal necrosis of the liver, and less congestion, edema, and emphysematous and inflammatory changes in the lung in the sepsis + CAPE group than in the other groups. These results support that CAPE may be used for the treatment of organ failure during sepsis.
...
PMID:Effects of caffeic acid phenethyl ester (CAPE) on sepsis in rats. 1860 6

The clinical features of PCP differ according to the factors responsible for the predisposing immunosuppression. Although the diagnosis of PCP often requires BAL, the profiles of the inflammatory mediators in the BAL fluid are not thoroughly documented. The aim of the current study was to characterize the profiles of inflammatory mediators in BAL fluid during PCP in patients with underlying autoimmune diseases, malignancies, or AIDS. The medical records of 14 patients with autoimmune diseases, 10 with malignancies, and 8 with AIDS, all of whom had been diagnosed with PCP by microscopic examination of BAL fluid, were reviewed. The concentrations of TNF-alpha, MCP-1, HMGB1, IL-8, IL-6, IL-10, and IFN-gamma in the BAL fluid that had been obtained for the diagnosis of PCP were measured. The concentrations of MCP-1, IL-8, and IL-6 differed according to the underlying disease, tending to be higher in patients with autoimmune diseases and lower in those with AIDS. The concentrations of HMGB1, IL-8, and IL-6 were positively correlated with the proportion of neutrophils in BAL fluid and inversely with the oxygenation index. Although the serum concentrations of CRP and LDH were positively correlated with those of IL-8 and MCP-1, none of the mediators in BAL fluid was correlated with the serum beta-D-glucan concentration. The production of inflammatory mediators in the lung differed between the patient groups with different underlying disorders. The modest upregulation of IL-8 and IL-6 might be associated with the milder clinical manifestations of PCP in AIDS patients.
...
PMID:Cytokine profiles of bronchoalveolar lavage fluid in patients with pneumocystis pneumonia. 2061 89


1 2 Next >>

---